Efficacy and Safety of the Aflibercept FYB203 Biosimilar in Comparison to Eylea® in Patients With Neovascular Age-Related Macular Degeneration (MAGELLAN-AMD)

A Phase 3 Randomized, Double-masked, Multicenter Study to Compare the Efficacy and Safety of the Proposed Aflibercept FYB203 Biosimilar in Comparison to Eylea® in Patients With Neovascular Age-Related Macular Degeneration

This is a randomized, double-masked, multicenter study to evaluate the efficacy and safety of FYB203 compared to Eylea® in patients with neovascular age related macular degeneration.

Study Overview

• Status: Completed
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Drug: FYB203 (Proposed aflibercept biosimilar); Drug: Eylea® (Aflibercept)

• Study Type: Interventional
• Enrollment (Actual): 434
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • Research Site
  • Stara Zagora, Bulgaria
    • Research Site
• Czechia
  • Hradec Králové, Czechia
    • Research Site
  • Ostrava, Czechia
    • Research Site
  • Pardubice, Czechia
    • Research Site
  • Prague, Czechia
    • Research Site
  • Sokolov, Czechia
    • Research Site
• Hungary
  • Budapest, Hungary
    • Research Site
  • Debrecen, Hungary
    • Research Site
  • Pécs, Hungary
    • Research Site
  • Szeged, Hungary
    • Research Site
  • Székesfehérvár, Hungary
    • Research Site
  • Tatabánya, Hungary
    • Research Site
  • Zalaegerszeg, Hungary
    • Research Site
• Israel
  • Haifa, Israel
    • Research Site
  • Jerusalem, Israel
    • Research Site
  • Kfar Saba, Israel
    • Research Site
  • Petah Tikva, Israel
    • Research Site
  • Rehovot, Israel
    • Research Site
  • Rishon LeZiyyon, Israel
    • Research Site
  • Tel Aviv, Israel
    • Research Site
• Italy
  • Bologna, Italy
    • Research Site
  • Florence, Italy
    • Research Site
  • Milan, Italy
    • Research Site
  • Roma, Italy
    • Research Site
  • Rozzano, Italy
    • Research Site
  • Udine, Italy
    • Research Site
• Japan
  • Akita, Japan
    • Research Site
  • Amagasaki, Japan
    • Research Site
  • Asahikawa, Japan
    • Research Site
  • Chiyoda City, Japan
    • Research Site
  • Chūō, Japan
    • Research Site
  • Fukuoka, Japan
    • Research Site
  • Fukushima, Japan
    • Research Site
  • Hamamatsu, Japan
    • Research Site
  • Himeji, Japan
    • Research Site
  • Hirakata, Japan
    • Research Site
  • Kita-ku, Japan
    • Research Site
  • Kurume, Japan
    • Research Site
  • Meguro City, Japan
    • Research Site
  • Nagasaki, Japan
    • Research Site
  • Nagoya, Japan
    • Research Site
  • Sapporo, Japan
    • Research Site
  • Shinjuku-Ku, Japan
    • Research Site
  • Suita, Japan
    • Research Site
  • Toride, Japan
    • Research Site
  • Yokosuka, Japan
    • Research Site
• Poland
  • Bielsko-Biala, Poland
    • Research Site
  • Bydgoszcz, Poland
    • Research Site
  • Krakow, Poland
    • Research Site
  • Lodz, Poland
    • Research Site
  • Olsztyn, Poland
    • Research Site
  • Tarnów, Poland
    • Research Site
  • Warsaw, Poland
    • Research Site
• Russia
  • Chelyabinsk, Russia
    • Research Site
  • Kazan', Russia
    • Research Site
  • Moscow, Russia
    • Research Site
  • Novosibirsk, Russia
    • Research Site
  • Saint Petersburg, Russia
    • Research Site
• Ukraine
  • Kharkiv, Ukraine
    • Research Site
  • Kherson, Ukraine
    • Research Site
  • Kropyvnytskyi, Ukraine
    • Research Site
  • Lutsk, Ukraine
    • Research Site
  • Odesa, Ukraine
    • Research Site
  • Poltava, Ukraine
    • Research Site
  • Zaporizhzhya, Ukraine
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 50 years at Screening.

• Male or female:

  • Male: A male patient must agree to use contraception as defined in this protocol during the treatment period and for at least 4 weeks after the last dose of study treatment.

  • Female: A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:

    1. Not a woman of childbearing potential (WOCBP), OR
    2. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 4 weeks after the last dose of study treatment.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Willingness and ability to undertake all scheduled visits and assessments.
• Newly diagnosed choroidal neovascularization (CNV) lesion secondary to wet AMD

Exclusion Criteria:

Patients are not eligible for the study if any of the following criteria apply:

• Employees of clinical study sites, individuals directly involved with the conduct of the study or immediate family members thereof, prisoners, and persons who are legally institutionalized.
• Study eye requiring immediate treatment.
• Any prior treatment with VEGF agent or any investigational products to treat AMD in either eye.
• Uncontrolled ocular hypertension or glaucoma in the SE (defined as intraocular pressure [IOP] ≥ 30 mmHg, despite treatment with anti-glaucomatous medication).
• Ocular disorders in the SE (i.e. retinal detachment, pre-retinal membrane of the macula or cataract with significant impact on VA) at the time of screening that may confound interpretation of study results and compromise VA.
• Any concurrent intraocular condition in the SE (e.g. glaucoma, cataract, or diabetic retinopathy) that, in the opinion of the Investigator, would either require surgical intervention during the study to prevent or treat visual loss that might result from that condition or affect interpretation of study results.
• Use of other investigational drugs (excluding vitamins, minerals) within 30 days or 5 half lives from randomization, whichever is longer.
• Any type of advanced, severe, or unstable disease, including any medical condition (controlled or uncontrolled) that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk.
• Stroke or myocardial infarction within 6 months prior to randomization.
• Known hypersensitivity to the IMP (aflibercept or any component of the aflibercept formulation) or to drugs of similar chemical class or to fluorescein or any other component of fluorescein formulation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FYB203 (Proposed aflibercept biosimilar); Patients will receive intravitreal (IVT) injections of FYB203 as detailed in the protocol.	Drug: FYB203 (Proposed aflibercept biosimilar); Patients will receive 1 IVT injection of FYB203 in the study eye only every 4 weeks for the first 3 consecutive doses, followed by 1 IVT injection every 8 weeks through study completion.
Active Comparator: Eylea® (Aflibercept); Patients will receive intravitreal (IVT) injections of Eylea® as detailed in the protocol.	Drug: Eylea® (Aflibercept); Patients will receive 1 IVT injection of Eylea® in the study eye only every 4 weeks for the first 3 consecutive doses, followed by 1 IVT injection every 8 weeks through study completion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate and Compare Functional Changes in Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Letters at Week 8 of Treatment With FYB203 or Eylea Compared to Baseline.	Changes in Best Corrected Visual Acuity (BCVA) by ETDRS letters from the Baseline Visit (Visit 1) to Week 8 (Visit 3) were assessed. This involved measuring the number of letters a participant could correctly read using the study eye on the ETDRS chart. An increase in the number of ETDRS letters from baseline signifies an improvement in visual acuity of the study eye. The change from baseline was calculated as the observed post-baseline value minus the baseline value.	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate and Compare Functional Changes of the Retina by BCVA Over Time	Change of BCVA by ETDRS letters over the whole study from Baseline Visit (Visit 1) to Week 24 (Visit 5) and Week 56 (Visit 9) - FAS	Through study completion, until Week 56 (Visit 9)
Evaluate and Compare Changes in Foveal Center Point (FCP) Retinal Thickness	Change from Baseline Visit (Visit 1) in foveal center point FCP retinal thickness to Week 4 (Visit 2), Week 24 (Visit 5) and Week 56 (Visit 9) - FAS	Through study completion, until Week 56 (Visit 9)
Evaluate and Compare the Proportion of Patients Who Gain or Lose ≥ 5, 10, and 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters Compared to Baseline	Proportion of patients who gain or lose ≥ 5, 10, or 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters from Baseline Visit (Visit 1) to Week 24 (Visit 5) and Week 56 (Visit 9) - FAS	Through study completion, until Week 56 (Week 9)
Evaluate and Compare the Absence of Disease Activity (Fluid-free Macula) Over Time	Percentage of patients with fluid-free macula at Baseline (Visit 1), Week 24 (Visit 5), Week 56 (Visit 9) - FAS	Through study completion, until Week 56 (Visit 9)
Evaluate and Compare Systemic Free Aflibercept Concentrations in a Subgroup of up to 60 Patients (up to 30 Per Arm)	Systemic concentrations (close to maximum concentration [Cmax]) of free aflibercept in a subgroup at selected sites - PKS: - 48 hours after the 3rd dose (Visit 3a)	At Baseline and Visit 3a (48 hours after the 3rd dose)
Evaluate and Compare Change in Vision-related Functioning and Well-being Measured by National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25)	Change from Baseline Visit (Visit 1) in vision-related functioning and well-being measured by National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) to Week 24 (Visit 5) and Week 56 (Visit 9) - FAS. The NEI VFQ-25 includes 12 subscales (e.g., general vision, ocular pain, driving, peripheral vision) scored from 0 to 100, where higher scores indicate better functioning. Subscales are averaged to produce a composite score, excluding the general health subscale. Both subscale and composite scores range from 0 (worst) to 100 (best), representing the percentage of the highest possible score achieved.	Through study completion, until Week 56 (Visit 9)
Evaluate and Compare the Immunogenic Profile (Anti-drug Antibodies [ADAs]) in Serum	Number of patients with anti-drug antibodies (ADAs) at Baseline (Visit 1), Week 24 (Visit 5) and Week 56 (Visit 9) - SAF	Through study completion, until Week 56 (Visit 9)
Frequency of Local and Systemic Adverse Events (AEs) and Serious Adverse Events (SAEs)	Frequency of local and systemic adverse events (AEs) and serious adverse events (SAEs) - SAF	Through study completion, until Week 56 (Visit 9)

Collaborators and Investigators

• Sponsor: Bioeq GmbH
• Investigators: Study Director: Study Official, Bioeq GmbH

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2020
• Primary Completion (Actual): June 23, 2022
• Study Completion (Actual): May 18, 2023

Study Registration Dates

• First Submitted: August 11, 2020
• First Submitted That Met QC Criteria: August 19, 2020
• First Posted (Actual): August 21, 2020

Study Record Updates

• Last Update Posted (Estimated): November 13, 2025
• Last Update Submitted That Met QC Criteria: October 31, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; aflibercept
• Other Study ID Numbers: FYB203-03-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes